Approach
Once a provisional diagnosis of kwashiorkor is made, the condition should be categorised as uncomplicated (amenable to outpatient therapy) or complicated (requiring facility-based care). A child's clinical presentation is the primary determinant of the decision, but available resources must also be considered. The decision to offer hospital care is based on clinical judgement and expert opinion. Complications and electrolyte status in kwashiorkor are difficult to identify either clinically or via laboratory investigation, so treatment should be based on a standardised protocol. Kwashiorkor can be classified as uncomplicated if the child passes an 'appetite test'. The child is asked to consume approximately 30 grams of ready-to-use therapeutic food (RUTF) under direct observation. If the child is able to eat this in a reasonable amount of time (15 minutes or less) and does not have any other obvious complications, the illness is most likely to be uncomplicated and can be treated at home.[46][47][48] Children with any complications, such as abnormal mental status, marked lethargy, decreased consciousness, a significant concomitant infection, or underlying illness, or those who fail the appetite test, should have complications urgently addressed and be referred for inpatient care as a case of complicated kwashiorkor.
Typically, less than 10% of children need facility-based care; for most children, home-based management is associated with equivalent or superior outcomes compared with hospital care. The World Health Organization (WHO), The United Nations Children’s Fund (UNICEF), and the World Food Programme (WFP) published a statement advocating home-based therapy over hospital care, where over-crowding causes frequent spread of infection.[48][49]
The goals of therapy are treating concomitant infections, resolving oedema, and raising the child's weight for height z-score to a level >-2 or mid upper-arm circumference (MUAC) to >125 mm (if either was low at the time of diagnosis). The z-score is defined as the deviation of the value from the median of the reference population, divided by the standard deviation of the reference population.
Optimising nutrition in uncomplicated kwashiorkor
A child with uncomplicated kwashiorkor can be treated at home with RUTF.[46][47] This paste-like therapeutic food is nutritionally equivalent to traditional milk-based diets and contains ample micro-nutrients for catch-up growth and replenishment of body stores, when given at 175 kcal/kg/day. The child should receive a supply of RUTF upon enrolment, and should return for follow-up at regular intervals (every 1-2 weeks) for progress to be assessed and for subsequent supplies of therapeutic food. If resources are limited or the child lives far from the health centre, it is reasonable to schedule follow-up every 4 weeks.[50]
Dietary therapy ceases when oedema has resolved for at least 1 week, and anthropometry and clinical assessment indicates a recovery to >-2 standard deviations below the mean weight for height and/or MUAC is ≥125 mm (depending on whether either or both were low at the time of admission). This is typically between 4 and 8 weeks after diagnosis. Food security should be ensured for the immediate post-discharge period, as recurrence is well recognised if the child returns to the same environment.
In the absence of a programme that can offer RUTF, patients are treated as for complicated malnutrition, as inpatients, usually with F-75 and F-100 formula feeds or locally made equivalents, until nutritional discharge criteria are met.[51]
Optimising nutrition in complicated kwashiorkor
A child with kwashiorkor in an immediately life-threatening condition should be stabilised in an inpatient facility. Hospital care involves feeding small amounts of a milk-based liquid food every 2-3 hours, with an initial recommended daily intake of 100 kcal/kg/day, increasing each day as tolerated.[1] Once the child's condition has stabilised and appetite has returned, the child is best managed in the same way as a child with uncomplicated malnutrition, at home, with dietary therapy. As appetite typically returns slowly, regulation of a child's dietary intake as the appetite returns at home is not necessary as long as the child consumes a minimum 100 kcal/kg/day.
Management of acute complications
Sepsis
All children with uncomplicated severe acute malnutrition should be treated with a broad-spectrum oral antibiotic, as sepsis, probably from bacterial translocation, is underappreciated. This recommendation is based on two large randomised, double-blind clinical trials conducted in rural Africa. Amoxicillin or cefdinir have been shown to be effective, and it is likely that other agents may also be effective.[52][53]
Sepsis occurs in 15% to 60% of children with complicated severe malnutrition, and it is standard practice to administer broad-spectrum parenteral antibiotics.[54] If specific infections are identified, specific treatment can be added. If blood cultures indicate resistance to the current treatment, therapy should be targeted accordingly.
Micronutrient deficiencies
Children aged 6-59 months with severe acute malnutrition should receive vitamin A supplementation throughout the treatment period, either within the therapeutic ready-to-use foods that comply with WHO specifications or as part of a multi-micronutrient formulation.[55][56]
Vitamin A (retinol) is given orally in a higher dose if there are any signs of xerophthalmia.[57]
Shock
Severely malnourished children should be monitored carefully for shock. It may result from cardiac failure, compromised capillary integrity, or, less commonly, fluid losses. Determining shock aetiology will guide treatment and influence outcome. Supplemental oxygen is given when possible. Often, clinicians are concerned that severely malnourished children have hypovolaemic shock from intravascular fluid depletion, because these children take oral fluids poorly, may have a few loose stools daily, and may have altered mental status. However, these symptoms may be seen in shock of any aetiology. Hypovolaemic shock is more likely if there are 6 stools a day or large volumes of watery stool.
Intravenous fluid infusions are rarely given to severely malnourished children. This treatment has been identified as a risk factor for death, even after controlling for the severity of the illness.[58] Standard management recommendations direct that isotonic parenteral fluids should only be given in cases of profuse watery diarrhoea and when the clinician is firmly convinced by clinical observation that shock is present. Recommencement of oral fluids and feeds as soon as tolerated is recommended.[54][59]
In the case of confirmed shock, resuscitation with intravenous fluids should be cautious (10-15 mL/kg/hour), assessing for response (reduced heart rate, reduced respiratory rate, improved capillary refill) or over-hydration (increasing heart rate, enlarging liver, increasing respiratory rate). After 2 hours the child should be re-assessed, and if there is an improvement, oral rehydration should be continued in quantities estimated to replace fluid losses, in addition to F-75 therapeutic milk.
The child should be considered for volume replacement with colloid solution or blood if not responding and not over-hydrated, as non-response may represent septic shock.
Dehydration
Accurate diagnosis is difficult in malnourished children.
For children with continual diarrhoea, management using a standardised oral rehydration protocol has been associated with a reduction in mortality.[59]
Rehydration Solution for Malnutrition (ReSoMal) is used for malnourished children with dehydration, both to achieve euvolaemia and to replace further ongoing gastrointestinal losses. It can be given either orally or via a nasogastric tube.[54] Standard WHO oral rehydration salts are too high in sodium (70 mmol/L of sodium) and too low in potassium to be given; these increase the risk of heart failure (sodium retention due to inability of the kidneys to adequately excrete the high sodium load in the setting of a heart muscle that is thin and atrophied in severely malnourished children).[29][30]
Between 70 and 100 mL of ReSoMal per kg of body weight is usually enough to rehydrate. It should be given orally or by nasogastric tube over 12 hours, starting with 5 mL/kg every 30 minutes for the first 2 hours, and then 5-10 mL/kg per hour (slower than for children who are not severely malnourished). The child should be reassessed at least every hour. The exact amount to give should be guided by how much the child will drink, the amount of ongoing losses from diarrhoea or vomiting, or any signs of overhydration, especially signs of heart failure. Overhydration is indicated by an elevated pulse rate (increase of ≥25 beats/minute) and respiratory rate (increase of ≥5 breaths/minute), engorged jugular veins, or increasing oedema (e.g., puffy eyelids).[1]
Rehydration therapy can be stopped when ≥ 3 of the following signs occur: the child is no longer thirsty, is passing urine, is less lethargic, the respiratory or pulse rates slow, skin pinch returns more quickly, and tears, moist eyes, moist mouth are present. However, many severely malnourished children will not show these signs even when hydrated.
Fluids given to maintain hydration should be based on the child's willingness to drink and, if possible, the amount of ongoing diarrhoea. In general, children under 2 years should receive 50-100 mL (between one-quarter and one-half of a large cup) of ReSoMal after each loose stool, while older children should have 100-200 mL, continued until diarrhoea stops.[1]
Hypoglycaemia
This is defined as a blood glucose <3 mmol/L (<54 mg/dL). To treat hypoglycaemia in a conscious child, a bolus feed of glucose or sucrose solution can be given. For an unconscious or convulsing child, 10% glucose, dextrose, or sucrose solution can be given intravenously or via a nasogastric tube. This is followed by a quarter amount of the 2-hourly feed every 30 minutes for the first 2 hours, continued until the blood glucose reaches 3 mmol/L.
Repeat blood glucose testing with finger/heel prick of blood is advised after 2 hours. Most children stabilise in 30 minutes, when 2-hourly feeds can be commenced. If unsuccessful, or if rectal temperature falls to <35.5°C (96°F) or level of consciousness deteriorates, treatment can be repeated.
Electrolyte imbalance
This is characteristic, though may not be reflected in serum biochemistry. Food should be prepared without salt, and additional F-75 rehydration fluid is recommended initially and ReSoMal if necessary. Phosphate- and potassium-rich diets are recommended.
Hypothermia
To prevent hypothermia, the child is kept dry, wrapped in blankets, and close to the mother's body. If the rectal temperature is <35.5°C (96°F), immediate feeding is advised while maintaining warmth and keeping the child close to the mother.
Dermatosis
If the nappy area is affected by dermatosis, it is best left uncovered. If dermatosis affects other areas, zinc oxide ointment or paraffin gauze dressings can help with analgesia and prevent infection. Affected areas should be bathed in 0.01% potassium permanganate for 10 minutes on a daily basis to help prevent infection, although antibiotics are also given.
Anaemia
Malnourished children often have a low haemoglobin, typically 80-100 g/L (8-10 g/dL). When in shock, malnourished children look pale; this may prompt the clinician to erroneously consider whether anaemia is the cause of their haemodynamic response.
Typically, anaemia does not compromise oxygen delivery to the tissues, and blood transfusions have been identified as a risk factor for heart failure. The WHO recommends giving blood transfusions only if haemoglobin is <40 g/L (4 g/dL) or there is cardiac failure secondary to anaemia. Oral iron is associated with poorer outcome, and should not be administered in the initial phase of treatment.[60]
Resistant patients or comorbid infections
If oedema fails to respond within 5-7 days and diarrhoea continues, the WHO recommends the addition of metronidazole if Giardia is identified in the stool.[1]
Tuberculosis (TB) should be considered; family history, chest x-ray, and TB skin testing are helpful although not always positive even in the presence of TB, particularly if there is also HIV infection. See Pulmonary tuberculosis.
Immunosuppressed children are at increased risk of opportunistic infections and are susceptible to atypical pathogens. Prophylactic trimethoprim/sulfamethoxazole is recommended if HIV infection is known or if exposure is suspected, particularly in an endemic area. Additionally, antiretroviral therapy should be considered if not already established but is also dependent on the availability of medication. See HIV infection.
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